There is no more vital sensory function than guiding and motivating the selection and consumption of safe and nutritious foods. Much of this function is carried-out by the sensory systems of the mouth and nose which together give rise to the flavor of foods. Although research has focused almost exclusively on the senses of taste and retronasal olfaction, also important are the thermal, mechanical, and chemesthetic components of flavor. The long-term goal of this project is therefore to understand in what ways and via which mechanisms somatosensory stimuli contribute to flavor perception. As in past funding periods, psychophysical studies in the current period have led to the discovery of previously unrecognized effects of temperature and touch on taste and chemesthesis. The proposed project will focus on differential effects of temperature on sweet taste, bitter taste, and oral chemesthesis that have implications for the molecular and cellular mechanisms of gustatory and chemesthetic transduction. Specifically, Aim 1 will test the hypothesis that temperature affects sweet taste primarily by modulating the rate and degree of adaptation, possibly by changes in conformation of the T1R2- T1R3 sweet taste receptor. Aim 2 will investigate the potential role of the cation channel TPRM5 in the perceptual phenomenon of Thermal Taste and its possible contribution to the counteraction of sweet taste adaptation. Aim 3 will investigate the differentia effects of temperature on bitter taste perception with the goal of determining the relationship of these effects to different modes of bitter taste transduction, including the possible contribution f TRPM5. Finally, Aim 4 will measure how temperature influences the taste and chemesthetic sensations of salts and acids with the specific goal of testing the hypothesis that their chemesthetic qualities are evoked primarily via different thermally-sensitive TRP channels (i.e. TRPV1 vs. TRPA1). Together these aims will lead to a more complete understanding of the ways in which temperature affects taste and flavor, while also providing unique tests of hypotheses about chemosensory mechanisms in humans that have been developed primarily in animal models. Translational research of this kind is therefore important for advancing our understanding of cellular and molecular mechanisms in humans that could lead to new strategies for addressing dysfunctions of taste and flavor that adversely affect diet and health.